Relative Reduction In Mortality Research Articles

Thromboembolism, bleeding and vascular death in nonvalvular atrial fibrillation patients with type 2 diabetes receiving rivaroxaban or warfarin

BackgroundDiabetes increases a patient’s risk of developing atrial fibrillation by 49%. Patients with nonvalvular atrial fibrillation are at a fivefold increased risk of stroke and die more frequently from vascular causes. We sought to evaluate the effectiveness and safety of rivaroxaban versus warfarin in nonvalvular atrial fibrillation patients with type 2 diabetes.MethodsThis was an analysis of Optum® De-Identified electronic health record data from 11/2010 to 12/2019. We included adults with nonvalvular atrial fibrillation and type 2 diabetes, newly started on rivaroxaban or warfarin and with ≥ 12-months of prior electronic health record activity. Patients who were pregnant, had alternative indications for oral anticoagulation or valvular heart disease were excluded. We evaluated the incidence rate (%/year) of developing the composite outcome of stroke/systemic embolism or vascular death and major or clinically relevant nonmajor bleeding as well as each endpoint individually. Hazard ratios with 95% confidence intervals were calculated using propensity score-overlap weighted proportional hazards regression.ResultsWe included 32,078 rivaroxaban (31% initiated on 15 mg dose) and 83,971warfarin users (time-in-therapeutic range = 47 ± 28%). Rivaroxaban was associated with a reduced risk of stroke/systemic embolism or vascular death (3.79 vs. 4.19; hazard ratio = 0.91, 95% confdience interval = 0.88–0.95), driven mostly by reductions in vascular death (2.81 vs 3.18, hazard ratio = 0.90, 95% confidence interval = 0.86–0.95) and systemic embolism (0.13 vs. 0.16; hazard ratio = 0.82, 95% confidence interval = 0.66–1.02). Major/clinically relevant nonmajor bleeding was less frequent with rivaroxaban versus warfarin (2.17 vs. 2.31; hazard ratio = 0.94, 95% confidence interval = 0.89–0.99) due to decreased critical organ bleeding (including intracranial hemorrhage) (0.35 vs. 0.54; hazard ratio = 0.63, 95% confidence interval = 0.55–0.72).ConclusionsIn nonvalvular atrial fibrillation patients with type 2 diabetes, rivaroxaban was associated with an ~ 10% relative reduction in vascular mortality and fewer bleeding-related hospitalizations versus warfarin.

Effect of screening by clinical breast examination on breast cancer incidence and mortality after 20 years: prospective, cluster randomised controlled trial in Mumbai

ObjectiveTo test the efficacy of screening by clinical breast examination in downstaging breast cancer at diagnosis and in reducing mortality from the disease, when compared with no screening.DesignProspective, cluster randomised...

Ablation Versus Drug Therapy for Atrial Fibrillation in Heart Failure: Results From the CABANA Trial.

In patients with heart failure and atrial fibrillation (AF), several clinical trials have reported improved outcomes, including freedom from AF recurrence, quality of life, and survival, with catheter ablation. This article describes the treatment-related outcomes of the AF patients with heart failure enrolled in the CABANA trial (Catheter Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation). The CABANA trial randomized 2204 patients with AF who were ≥65 years old or <65 years old with ≥1 risk factor for stroke at 126 sites to ablation with pulmonary vein isolation or drug therapy including rate or rhythm control drugs. Of these, 778 (35%) had New York Heart Association class >II at baseline and form the subject of this article. The CABANA trial's primary end point was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Of the 778 patients with heart failure enrolled in CABANA, 378 were assigned to ablation and 400 to drug therapy. Ejection fraction at baseline was available for 571 patients (73.0%), and 9.3% of these had an ejection fraction <40%, whereas 11.7% had ejection fractions between 40% and 50%. In the intention-to-treat analysis, the ablation arm had a 36% relative reduction in the primary composite end point (hazard ratio, 0.64 [95% CI, 0.41-0.99]) and a 43% relative reduction in all-cause mortality (hazard ratio, 0.57 [95% CI, 0.33-0.96]) compared with drug therapy alone over a median follow-up of 48.5 months. AF recurrence was decreased with ablation (hazard ratio, 0.56 [95% CI, 0.42-0.74]). The adjusted mean difference for the AFEQT (Atrial Fibrillation Effect on Quality of Life) summary score averaged over the entire 60-month follow-up was 5.0 points, favoring the ablation arm (95% CI, 2.5-7.4 points), and the MAFSI (Mayo Atrial Fibrillation-Specific Symptom Inventory) frequency score difference was -2.0 points, favoring ablation (95% CI, -2.9 to -1.2). In patients with AF enrolled in the CABANA trial who had clinically diagnosed stable heart failure at trial entry, catheter ablation produced clinically important improvements in survival, freedom from AF recurrence, and quality of life relative to drug therapy. These results, obtained in a cohort most of whom had preserved left ventricular function, require independent trial verification. Registration: URL: https://www.clinicaltrials.gov/ct2/show/NCT00911508; Unique identifier: NCT0091150.

Randomized Blinded Placebo-Controlled Trials of Renal Sympathetic Denervation for Hypertension: A Meta-Analysis

BackgroundThe efficacy of renal denervation has been controversial, but the procedure has now undergone several placebo-controlled trials. New placebo-controlled trial data has recently emerged, with longer follow-up of one trial and the full report of another trial (which constitutes 27% of the total placebo-controlled trial data). We therefore sought to evaluate the effect of renal denervation on ambulatory and office blood pressures in patients with hypertension. MethodsWe systematically identified all blinded placebo-controlled randomized trials of catheter-based renal denervation for hypertension. The primary efficacy outcome was ambulatory systolic blood pressure change relative to placebo. A random-effects meta-analysis was performed. Results6 studies randomizing 1232 patients were eligible. 713 patients were randomized to renal denervation and 519 to placebo. Renal denervation significantly reduced ambulatory systolic blood pressure (−3.52 mmHg; 95% CI −4.94 to −2.09; p < 0.0001), ambulatory diastolic blood pressure (−1.93 mmHg; 95% CI −3.04 to −0.83, p = 0.0006), office systolic blood pressure size (−5.10 mmHg; 95% CI −7.31 to −2.90, p < 0.0001) and office diastolic pressure (effect size −3.11 mmHg; 95% CI −4.43 to −1.78, p < 0.0001). Adverse events were rare and not more common with denervation. ConclusionsThe totality of blinded, randomized placebo-controlled data shows that renal denervation is safe and provides genuine reduction in blood pressure for at least 6 months post-procedure. If this effect continues in the long term, renal denervation might provide a life-long 10% relative risk reduction in major adverse cardiac events and 7.5% relative risk reduction in all-cause mortality.

A nationwide observational cohort study of the relationship between beta-blockade and survival after hip fracture surgery

PurposeDespite advances in the care of hip fractures, this area of surgery is associated with high postoperative mortality. Downregulating circulating catecholamines, released as a response to traumatic injury and surgical trauma, is believed to reduce the risk of death in noncardiac surgical patients. This effect has not been studied in hip fractures. This study aims to assess whether survival benefits are gained by reducing the effects of the hyper-adrenergic state with beta-blocker therapy in patients undergoing emergency hip fracture surgery.MethodsThis is a retrospective nationwide observational cohort study. All adults ge 18 years were identified from the prospectively collected national quality register for hip fractures in Sweden during a 10-year period. Pathological fractures were excluded. The cohort was subdivided into beta-blocker users and non-users. Poisson regression with robust standard errors and adjustments for confounders was used to evaluate 30-day mortality.Results134,915 patients were included of whom 38.9% had ongoing beta-blocker therapy at the time of surgery. Beta-blocker users were significantly older and less fit for surgery. Crude 30-day all-cause mortality was significantly increased in non-users (10.0% versus 3.7%, p < 0.001). Beta-blocker therapy resulted in a 72% relative risk reduction in 30-day all-cause mortality (incidence rate ratio 0.28, 95% CI 0.26–0.29, p < 0.001) and was independently associated with a reduction in deaths of cardiovascular, respiratory, and cerebrovascular origin and deaths due to sepsis or multiorgan failure.ConclusionsBeta-blockers are associated with significant survival benefits when undergoing emergency hip fracture surgery. Outlined results strongly encourage an interventional design to validate the observed relationship.

Predicting difference in mean survival time from cause-specific hazard ratios for women diagnosed with breast cancer.

Relative reduction in breast cancer mortality is the preferred outcome measure for evaluation of mammography screening. However, mean survival time has been advocated as a better and more intuitive outcome for risk communication. We have previously introduced a method to predict difference in mean survival time from empirical hazard ratios for all-cause mortality. In this article, we aim to investigate the association between hazard ratios for breast cancer mortality and the difference in mean survival time for women diagnosed with breast cancer. We retrieved data on all women diagnosed with first-time invasive breast cancer in Norway from 1960 through 2004. Women were followed until emigration or end of follow-up on 31 December 2015, whichever came first. Observed differences in mean survival times and hazard ratios for both breast cancer death and death from causes other than breast cancer were obtained for neighbouring time periods defined by women's age and year of diagnosis. Based on previously developed methods, we fitted a linear relationship between observed differences in mean survival and logarithmic hazard ratios. A linear association was found between breast cancer-specific hazard ratios and difference in mean survival time for women diagnosed with breast cancer. This association was also estimated with adjustment for other causes of death than breast cancer. The change in mean survival time could be predicted from an estimated reduction in breast cancer mortality. This outcome measure can contribute to better and more understandable risk information about the effect of mammography screening programmes.

Temporal Trends in Hemoglobin, Use of Erythropoiesis Stimulating Agents, and Major Clinical Outcomes in Incident Dialysis Patients in Canada

IntroductionSeveral jurisdictions have adopted a more conservative approach to anemia in patients receiving dialysis amid safety concerns from target hemoglobin studies. It is largely unknown if this has contributed to a change in clinical outcomes.MethodsA national registry was used to identify 35,945 adult patients who initiated and were maintained on dialysis for ≥90 days in Canada from January 2007 to December 2015. Outcomes were ascertained until March 2017 via linkage with hospital discharge diagnoses. Cox proportional hazards models were used to investigate the association between the era of dialysis initiation and the primary composite outcome (acute myocardial infarction [AMI], stroke, or mortality).ResultsThe mean hemoglobin at dialysis initiation decreased from 102.9 g/l in 2007 to 95.5 g/l in 2015, corresponding with a higher prevalence of hemoglobin <80 g/l (8% to 17%) and a reduction in erythropoiesis stimulating agent (ESA) use (49% to 44%). After multivariable adjustment, Era 3 (2013–2015) was associated with an 8% relative risk reduction in the primary outcome compared with Era 1 (2007–2009) (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.88–0.96), a 10% relative reduction in mortality (HR 0.90, 95% CI 0.85–0.94) but no significant change in AMI or stroke. In a model without era, neither hemoglobin nor ESA use was an independent predictor of outcome.ConclusionThere have been modest declines in average hemoglobin values and ESA use among incident dialysis patients in Canada with no change in major cardiovascular outcomes. Patient survival has improved over time, likely for reasons other than anemia management.

Biomarkers in lung cancer screening: a narrative review

: Although when used as a lung cancer screening tool low-dose computed tomography (LDCT) has demonstrated a significant reduction in lung cancer related mortality, it is not without pitfalls. The associated high false positive rate, inability to distinguish between benign and malignant nodules, cumulative radiation exposure, and resulting patient anxiety have all demonstrated the need for adjunctive testing in lung cancer screening. Current research focuses on developing liquid biomarkers to complement imaging as non-invasive lung cancer diagnostics. Biomarkers can be useful for both the early detection and diagnosis of disease, thereby decreasing the number of unnecessary radiologic tests performed. Biomarkers can stratify cancer risk to further enrich the screening population and augment existing risk prediction. Finally, biomarkers can be used to distinguish benign from malignant nodules in lung cancer screening. While many biomarkers require further validation studies, several, including autoantibodies and blood protein profiling, are available for clinical use. This paper describes the need for biomarkers as a lung cancer screening tool, both in terms of diagnosis and risk assessment. Additionally, this paper will discuss the goals of biomarker use, describe properties of a good biomarker, and review several of the most promising biomarkers currently being studied including autoantibodies, complement fragments, microRNA, blood proteins, circulating tumor DNA (ctDNA), and DNA methylation. Finally, we will describe future directions in the field of biomarker development.

Comparison of cost-effectiveness of implantable cardioverter defibrillator therapy in patients for primary prevention in Latin America: an analysis using the Improve SCA study

Objective The mortality benefit of implantable cardioverter defibrillators (ICDs) for primary prevention (PP) of sudden cardiac arrest (SCA) has been well-established, but ICD therapy remains globally underutilized. The results of the Improve SCA study showed a 49% relative risk reduction in all-cause mortality among ICD patients with 1.5 primary prevention (1.5PP) characteristics (patients with one or more risk factors, p < 0.0001). We evaluated the cost-effectiveness of ICD compared to no ICD therapy among patients with 1.5PP characteristics in three Latin American countries and analyzed the factors involved in cost-effectiveness. Methods We used a published Markov model that compares costs and outcomes of ICD to no ICD therapy from local payers’ perspective and included country-specific and disease-specific inputs from the Improve SCA study and current literature. We used WHO-recommended willingness-to-pay (WTP) thresholds to assess cost-effectiveness and compared model outcomes between countries. Results Incremental costs per QALY (quality-adjusted life year) saved by ICD compared to no ICD therapy are Colombian Pesos COP$46,729,026 in Colombia, Mexican Pesos MXN$246,016 in Mexico, and Uruguayan Pesos UYU$1,213,614 in Uruguay in the base case scenario; all three figures are between 1–3-times GDP per capita for each country. One-way and probabilistic sensitivity analyses confirm the base case scenario results. Non-cardiac accumulated deaths are lower in Mexico, resulting in a comparatively increased cost-effective ICD therapy. Limitations The Improve SCA study was not randomized, so clinical results could be biased; however, measures were taken to reduce this bias. Costs and benefits were modelled beyond the timeline of direct observation in the Improve SCA study. Conclusions ICD therapy is cost-effective in Mexico and Uruguay and potentially cost-effective in Colombia for a 1.5PP population. Variability in ICER estimates by country can be explained by differences in non-cardiac deaths and cost inputs.

Comparing COVID-19 vaccine allocation strategies in India: A mathematical modelling study

BackgroundThe development and widespread use of an effective SARS-CoV-2 vaccine could prevent substantial morbidity and mortality associated with COVID-19 and mitigate the secondary effects associated with non-pharmaceutical interventions. MethodsWe used an age-structured, expanded SEIR model with social contact matrices to assess age-specific vaccine allocation strategies in India. We used state-specific age structures and disease transmission coefficients estimated from confirmed incident cases of COVID-19 between 1 July and 31 August 2020. Simulations were used to investigate the relative reduction in mortality and morbidity of vaccine allocation strategies based on prioritizing different age groups, and the interactions of these strategies with concurrent non-pharmaceutical interventions. Given the uncertainty associated with COVID-19 vaccine development, we varied vaccine characteristics in the modelling simulations. ResultsPrioritizing COVID-19 vaccine allocation for older populations (i.e., >60 years) led to the greatest relative reduction in deaths, regardless of vaccine efficacy, control measures, rollout speed, or immunity dynamics. Preferential vaccination of this group often produced relatively higher total symptomatic infections and more pronounced estimates of peak incidence than other assessed strategies. Vaccine efficacy, immunity type, target coverage, and rollout speed significantly influenced overall strategy effectiveness, with the time taken to reach target coverage significantly affecting the relative mortality benefit comparative to no vaccination. ConclusionsOur findings support global recommendations to prioritize COVID-19 vaccine allocation for older age groups. Relative differences between allocation strategies were reduced as the speed of vaccine rollout was increased. Optimal vaccine allocation strategies will depend on vaccine characteristics, strength of concurrent non-pharmaceutical interventions, and region-specific goals.

Attributable Mortality of Ventilator-associated Pneumonia. Replicating Findings, Revisiting Methods

Rationale: Estimating the impact of ventilator-associated pneumonia (VAP) from routinely collected intensive care unit (ICU) data is methodologically challenging.Objectives: We aim to replicate earlier findings of limited VAP-attributable ICU mortality in an independent cohort. By refining statistical analyses, we gradually tackle different sources of bias.Methods: Records of 2,720 adult patients admitted to Ghent University Hospital ICUs (2013–2017) and receiving mechanical ventilation within 48 hours after admission were extracted from linked Intensive Care Information System and Computer-based Surveillance and Alerting of Nosocomial Infections, Antimicrobial Resistance, and Antibiotic Consumption in the ICU databases. The VAP-attributable fraction of ICU mortality was estimated using a competing risk analysis that is restricted to VAP-free patients (approach 1), accounts for VAP onset by treating it as either a competing (approach 2) or censoring event (approach 3), or additionally adjusts for time-dependent confounding via inverse probability weighting (approach 4).Results: A total of 210 patients (7.7%) acquired VAP. Based on benchmark approach 4, we estimated that (compared with current preventive measures) hypothetical eradication of VAP would lead to a relative ICU mortality reduction of 1.7% (95% confidence interval, −1.3 to 4.6) by Day 10 and of 3.6% (95% confidence interval, 0.7 to 6.5) by Day 60. Approaches 1–3 produced estimates ranging from −0.7% to 2.5% by Day 10 and from 5.2% to 5.5% by Day 60.Conclusions: In line with previous studies using appropriate methodology, we found limited VAP-attributable ICU mortality given current state-of-the-art VAP prevention measures. Our study illustrates that inappropriate accounting of the time dependency of exposure and confounding of its effects may misleadingly suggest protective effects of early-onset VAP and systematically overestimate attributable mortality.

The Association Between the Mediterranean Lifestyle Index and All-Cause Mortality in the Seguimiento Universidad de Navarra Cohort

Overall lifestyle patterns rather than individual factors may exert greater reductions on chronic disease risk and mortality. The objective is to study the association between a Mediterranean lifestyle index and all-cause and cause-specific mortality. Investigators analyzed data from 20,494 participants in the Seguimiento Universidad de Navarra cohort in 2019. The Mediterranean lifestyle index is composed of 28 items on food consumption, dietary habits, physical activity, rest, and social interactions that score 0 or 1 point; scores theoretically could range from 0 to 28 points. After a median follow-up of 12.1 years, 407 deaths were observed. In the multivariable-adjusted model, high adherence (>14 points) to the Mediterranean lifestyle was associated with a 41% relative reduction in all-cause mortality (hazard ratio=0.59, 95% CI=0.42, 0.83) compared with low adherence (3-10 points, p<0.001 for trend). For each additional point, the multivariable hazard ratios for all-cause mortality were 0.95 (95% CI=0.89, 1.02) for food consumption; 1.00 (95% CI=0.92, 1.08) for dietary habits; and 0.73 (95% CI=0.66, 0.80) for physical activity, rest, social habits, and conviviality. Significant interaction with age at last contact (p<0.001) suggested a lower risk for each additional point among participants aged ≥50 years (hazard ratio=0.50, 95% CI=0.34, 0.74), whereas no association was found for participants aged <50 years (hazard ratio=1.15, 95% CI=0.54, 2.44). Adherence to a Mediterranean lifestyle may reduce the risk of mortality in a Spanish cohort of university graduates. Inverse associations were found for the overall Mediterranean lifestyle score and lifestyle block, whereas no associations were observed for the dietary blocks. Future research should consider the Mediterranean lifestyle beyond the Mediterranean diet in different populations for the promotion of healthy longevity. This study is registered at www.clinicaltrials.gov NCT02669602.

Abstract 14992: Should Patients With Heart Failure With Reduced Ejection Fraction (HFrEF) be Discharged on Sacubitril/Valsartan or ACEi/ARB: A Decision Analysis Approach

Introduction: In the PARADIGM-HF study, sacubitril/valsartan demonstrated a 16% decrease in all-cause mortality and a 21% decrease in heart failure hospitalization. Cost and concern for a higher risk of side effects especially among older patients may have delayed early diffusion. This study aims to use a decision analysis approach to determine whether discharged on sacubitril/valsartan or ACEi/ARB is optimal after heart failure with reduced rejection fraction (HFrEF) hospitalization and whether this varies by age. Hypothesis: Discharge on sacubitril/valsartan will be associated with lower mortality and readmission rates across all age groups. Methods: We used an absorbing Markov chain simulation model with 1-month cycle length to determine the association between discharge on sacubitril/valsartan vs. ACEi/ARB and survival. We used a random 40% sample of Medicare A, B and D data from 2016-2017 to create a population of HFrEF patients (n=694,149) to determine the probabilities of drug discontinuation and adverse events. We used estimates from the PARADIGM-HF study to define the relative reduction in mortality and readmission rates with sacubitril/valsartan. Results: Among all patients, we found a 3.24 month survival advantage to discharge on sacubitril/valsartan. Among those aged 64-74, there was a 5.85 month survival advantage. Among those aged 74-85, there as a 3.47 month survival and among those aged 85+ there was a 1.38 month survival advantage ( Figure ). Conclusion: Among patients of all ages with HFrEF, there is a survival advantage to discharge on sacubitril/valsartan over ACEi/ARB but the magnitude of this benefit decreases with increasing age.

Characteristics and Effectiveness of Dedicated Care Programs for Patients Starting Dialysis: A Systematic Review.

Dedicated care programs that provide increased support to patients starting dialysis are increasingly being used to reduce the risk of complications. The objectives of this systematic review were to determine the characteristics of existing programs and their effect on patient outcomes. We searched Embase, MEDLINE, Web of Science, Cochrane CENTRAL, and CINAHL from database inception to November 20, 2019 for English-language studies that evaluated dedicated care programs for adults starting maintenance dialysis in the inpatient or outpatient setting. Any study design was eligible, but we required the presence of a control group and prespecified patient outcomes. We extracted data describing the nature of the interventions, their components, and the reported benefits. The literature search yielded 12,681 studies. We evaluated 66 full texts and included 11 studies (n=6812 intervention patients); eight of the studies evaluated hemodialysis programs. All studies were observational, and there were no randomized controlled trials. The most common interventions included patient education (n=11) and case management (n=5), with nurses involved in nine programs. The most common outcomes were mortality (n=8) and vascular access (n=4), with only three studies reporting on the uptake of home dialysis and none on transplantation. We identified four high-quality studies that combined patient education and case management; in these programs, the relative reduction in 90-day mortality ranged from 22% (95% CI, -3% to 41%) to 49% (95% CI, 33% to 61%). Pooled analysis was not possible due to study heterogeneity. Few studies have evaluated dedicated care programs for patients starting dialysis, especially their effect on home dialysis and transplantation. Whereas multidisciplinary care models that combine patient education with case management appear to be promising, additional prospective studies that involve patients in their design and execution are needed before widespread implementation of these resource-intensive programs.

Effect of Extracorporeal Blood Purification on Mortality in Sepsis: A Meta-Analysis and Trial Sequential Analysis

Objective: The objective of this study was to conduct a meta-analysis and trial sequential analysis (TSA) of published randomized controlled trials (RCTs) to determine whether mortality benefit exists for extracorporeal blood purification techniques in sepsis. Data Sources: A systematic search on MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for RCTs was performed. Study Selection: RCTs investigating the effect of extracorporeal blood purification device use on mortality among critically ill septic patients were selected. Data Extraction: Mortality was assessed using Mantel-Haenszel models, and I2 was used for heterogeneity. Data are presented as odds ratios (OR); 95% confidence intervals (CIs); p values; I2. Using the control event mortality proportion, we performed a TSA and calculated the required information size using an anticipated intervention effect of a 14% relative reduction in mortality. Data Synthesis: Thirty-nine RCTs were identified, with 2,729 patients. Fourteen studies used hemofiltration (n = 789), 17 used endotoxin adsorption devices (n = 1,363), 3 used nonspecific adsorption (n = 110), 2 were cytokine removal devices (n = 117), 2 used coupled plasma filtration adsorption (CPFA) (n = 207), 2 combined hemofiltration and perfusion (n = 40), and 1 used plasma exchange (n = 106). On conventional meta-analysis, hemofiltration (OR 0.56 [0.40–0.79]; p < 0.001; I2 = 0%), endotoxin removal devices (OR 0.40 [0.23–0.67], p < 0.001; I2 = 71%), and nonspecific adsorption devices (OR 0.32 [0.13–0.82]; p = 0.02; I2 = 23%) were associated with mortality benefit, but not cytokine removal (OR 0.99 [0.07–13.42], p = 0.99; I2 = 64%), CPFA (OR 0.50 [0.10–2.47]; p = 0.40; I2 = 64%), or combined hemofiltration and adsorption (OR 0.71 [0.13–3.79]; p = 0.69; I2 = 0%). TSA however revealed that based on the number of existing patients recruited for RCTs, neither hemofiltration (TSA-adjusted CI 0.29–1.10), endotoxin removal devices (CI 0.05–3.40), nor nonspecific adsorption devices (CI 0.01–14.31) were associated with mortality benefit. Conclusion: There are inadequate data at present to conclude that the use of extracorporeal blood purification techniques in sepsis is beneficial. Further adequately powered RCTs are required to confirm any potential mortality benefit, which may be most evident in patients at greatest risk of death.

Differences in rates of low-dose computed tomography screening for lung cancer amongst various outpatient care centers.

245 Background: Despite low-dose computed tomography (LDCT) screening for lung cancer recommended by the United States Preventive Services Task Force (USPSTF) demonstrating a relative reduction in mortality, there remains low rates of testing nationwide. Yet studies are limited regarding specific differences in screening rates amongst various outpatient care settings. Methods: We performed retrospective chart reviews of patients followed by resident providers within an academic internal medicine residency program who met USPSTF guidelines for lung cancer screening between 2015-2020. This was conducted at three separate outpatient clinic sites including a state-funded academic institution, inner city community health center, and veteran affairs medical center. Data collection included patient demographic and smoking histories as well as rates of ordered and completed LDCT screening. Results: A total of 832 patients were identified as current or former smokers between the ages of 55 and 80 years: 320 from Hartford Hospital Community Health Center (HHCHC), 262 from University of Connecticut Health Center (UCHC), and 250 from the Veteran Affairs (VA) Medical Center. 85 (27%) of these patients from HHCHC, 84 (32%) from UCHC, and 56 (22%) from the VA met USPSTF eligibility criteria for LDCT screening. Overall compliance rates of screening were found to be 44% at HHCHC, 59.5% at UCHC, and 51.8% at the VA. Results are outlined in Table. Conclusions: Screening rates for lung cancer with LDCT remain low but have been steadily improving throughout the United States following new recommendations and increased awareness provided by multiple medical organizations. We sought to compare differences in compliance rates amongst various outpatient clinics within the same internal medicine residency program at University of Connecticut. Our findings demonstrate significant differences in LDCT screening for lung cancer between the program’s community health center versus its state and federally funded outpatient clinics. Automatic reminders to providers can potentially improve rates of lung cancer screening. Patients should also be educated about the importance of screening to improve adherence with imaging. [Table: see text]

The initial validation of a novel outcome measure in severe burns- the Persistent Organ Dysfunction +Death: Results from a multicenter evaluation

IntroductionA need exists to improve the efficiency of clinical trials in burn care. The objective of this study was to validate “Persistent Organ Dysfunction” plus death as endpoint in burn patients and to demonstrate its statistical efficiency. MethodsThis secondary outcome analysis of a dataset from a prospective international multicenter RCT (RE-ENERGIZE) included patients with burned total body surface area >20% and a 6-month follow-up. Persistent organ dysfunction was defined as persistence of organ dysfunction with life-supportiing technologies and ICU care. ResultsIn the 539 included patients, the prevalence of 0p p+ pdeath was 40% at day 14 and of 27% at day 28. At both timepoints, survivors with POD (vs. survivors without POD) had a higher mortality rate, longer ICU- and hospital-stays, and a reduced quality of life. POD + death as an endpoint could result in reduced sample size requirements for clinical trials. Detecting a 25% relative risk reduction in 28-day mortality would require a sample size of 4492 patients, whereas 1236 patients would be required were 28-day POD + death used. ConclusionsPOD + death represents a promising composite outcome measure that may reduce the sample size requirements of clinical trials in severe burns patients. Further validation in larger clinical trials is warranted. Study typeProspective cohort study, level of evidence: II

Annual mammographic screening to reduce breast cancer mortality in women from age 40 years: long-term follow-up of the UK Age RCT.

There remains disagreement on the long-term effect of mammographic screening in women aged 40-49 years. The long-term follow-up of a randomised controlled trial that offered annual mammography to women aged 40-49 years. The estimation of the effect of these mammograms on breast cancer and other-cause mortality, and the effect on incidence, with implications for overdiagnosis. An individually randomised controlled trial comparing offering annual mammography with offering usual care in those aged 40-48 years, and thus evaluating the effect of annual screening entirely taking place before the age of 50 years. There was follow-up for an average of 23 years for breast cancer incidence, breast cancer death and death from other causes. We analysed the mortality and incidence data by Poisson regression and estimated overdiagnosis formally using Markov process models. Twenty-three screening units in England, Wales and Scotland within the NHS Breast Screening Programme. Women aged 39-41 years were recruited between 1990 and 1997. After exclusions, a total of 53,883 women were randomised to undergo screening (the intervention group) and 106,953 women were randomised to have usual care (the control group). The intervention group was invited to an annual breast screen with film mammography, two view at first screen and single view thereafter, up to and including the calendar year of their 48th birthday. The control group received no intervention. Both groups were invited to the National Programme from the age of 50 years, when screening is offered to all women in the UK. The main outcome measures were mortality from breast cancers diagnosed during the intervention phase of the trial (i.e. before the first National Programme screen at 50 years), mortality from all breast cancers diagnosed after randomisation, all-cause mortality, mortality from causes other than breast cancer, and the incidence of breast cancer. There was a statistically significant 25% reduction in mortality from breast cancers diagnosed during the intervention phase at 10 years' follow-up (relative rate 0.75, 95% confidence interval 0.58 to 0.97; p = 0.03). No reduction was observed thereafter (relative rate 0.98, 95% confidence interval 0.79 to 1.22). Overall, there was a statistically non-significant 12% reduction (relative rate 0.88, 95% confidence interval 0.74 to 1.03; p = 0.1). The absolute benefit remained approximately constant over time, at one death prevented per 1000 women screened. There was no effect of intervention on other-cause mortality (relative rate 1.02, 95% confidence interval 0.97 to 1.07; p = 0.4). The intervention group had a higher incidence of breast cancer than the control group during the intervention phase of the trial, but incidence equalised immediately on the first National Programme screen at the age of 50-52 years. There was 31% average non-compliance with screening and three centres had to cease screening for resource and capacity reasons. Annual mammographic screening at the age of 40-49 years resulted in a relative reduction in mortality, which was attenuated after 10 years. It is likely that digital mammography with two views at all screens, as practised now, could improve this further. There was no evidence of overdiagnosis in addition to that which already results from the National Programme carried out at later ages. There is a need for research on the effects of modern mammographic protocols and additional imaging in this age group. Current Controlled Trials ISRCTN24647151. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 55. See the NIHR Journals Library website for further project information. Other funding in the past has been received from the Medical Research Council, Cancer Research UK, the Department of Health and Social Care, the US National Cancer Institute and the American Cancer Society.

Levosimendan and Global Longitudinal Strain Assessment in Sepsis (GLASSES 1): a study protocol for an observational study

IntroductionCardiogenic shock is a condition of low cardiac output that represents the end stage of a progressive deterioration of cardiac function. The main cause is ischaemic heart disease, but there...

Effect of mammographic screening from age 40 years on breast cancer mortality (UK Age trial): final results of a randomised, controlled trial.

SummaryBackgroundThe appropriate age range for breast cancer screening remains a matter of debate. We aimed to estimate the effect of mammographic screening at ages 40–48 years on breast cancer mortality.MethodsWe did a randomised, controlled trial involving 23 breast screening units across Great Britain. We randomly assigned women aged 39–41 years, using individual randomisation, stratified by general practice, in a 1:2 ratio, to yearly mammographic screening from the year of inclusion in the trial up to and including the calendar year that they reached age 48 years (intervention group), or to standard care of no screening until the invitation to their first National Health Service Breast Screening Programme (NHSBSP) screen at approximately age 50 years (control group). Women in the intervention group were recruited by postal invitation. Women in the control group were unaware of the study. The primary endpoint was mortality from breast cancers (with breast cancer coded as the underlying cause of death) diagnosed during the intervention period, before the participant's first NHSBSP screen. To study the timing of the mortality effect, we analysed the results in different follow-up periods. Women were included in the primary comparison regardless of compliance with randomisation status (intention-to-treat analysis). This Article reports on long-term follow-up analysis. The trial is registered with the ISRCTN registry, ISRCTN24647151.Findings160 921 women were recruited between Oct 14, 1990, and Sept 24, 1997. 53 883 women (33·5%) were randomly assigned to the intervention group and 106 953 (66·5%) to the control group. Between randomisation and Feb 28, 2017, women were followed up for a median of 22·8 years (IQR 21·8–24·0). We observed a significant reduction in breast cancer mortality at 10 years of follow-up, with 83 breast cancer deaths in the intervention group versus 219 in the control group (relative rate [RR] 0·75 [95% CI 0·58–0·97]; p=0·029). No significant reduction was observed thereafter, with 126 deaths versus 255 deaths occurring after more than 10 years of follow-up (RR 0·98 [0·79–1·22]; p=0·86).InterpretationYearly mammography before age 50 years, commencing at age 40 or 41 years, was associated with a relative reduction in breast cancer mortality, which was attenuated after 10 years, although the absolute reduction remained constant. Reducing the lower age limit for screening from 50 to 40 years could potentially reduce breast cancer mortality.FundingNational Institute for Health Research Health Technology Assessment programme.